Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque

Abstract Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but the underlying molecular interactions remain unclear. This study aims to identify the molecular me...

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Main Authors: Ning Zhao, Dan Liu, Haixu Song, Xiaolin Zhang, Chenghui Yan, Yaling Han
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-83925-z
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author Ning Zhao
Dan Liu
Haixu Song
Xiaolin Zhang
Chenghui Yan
Yaling Han
author_facet Ning Zhao
Dan Liu
Haixu Song
Xiaolin Zhang
Chenghui Yan
Yaling Han
author_sort Ning Zhao
collection DOAJ
description Abstract Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but the underlying molecular interactions remain unclear. This study aims to identify the molecular mechanisms of ERS in AS pathogenesis to inform innovative diagnostic approaches and therapeutic targets for managing AS. GSE28829 and GSE43292—human early and advanced carotid atherosclerotic tissue samples—were obtained from the Gene Expression Omnibus database. Endoplasmic reticulum stress-related genes (ERSRGs) were obtained from GeneCards. Differential gene expression and weighted gene co-expression network analyses were conducted to identify genes associated with atherosclerosis, and intersection with ER-related genes revealed three ERSRGs (i.e. CTSB, LYN, and CYBB) associated with advanced atherosclerotic plaque. These three ERSRGs exhibited associations with various immune cells. Additionally, the three ERSRGs were upregulated in human atherosclerotic tissues, mouse models of progressive atherosclerotic lesions, and in vitro macrophage models. In conclusion, this study identified CTSB, LYN, and CYBB as potentially critical ERSRGs associated with advanced atherosclerotic plaque, demonstrating their good diagnostic utility and offering novel insights into the potential pathobiology of AS progression, paving the way for exploring innovative therapeutic targets.
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spelling doaj-art-4a7e4df444e34b68a5f01c1e3e7fcefb2025-01-19T12:20:56ZengNature PortfolioScientific Reports2045-23222025-01-0115112310.1038/s41598-024-83925-zIdentification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaqueNing Zhao0Dan Liu1Haixu Song2Xiaolin Zhang3Chenghui Yan4Yaling Han5Department of Cardiology, Second Norman Bethune Hospital of Jilin UniversityState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute, Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute, Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute, Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute, Department of Cardiology, General Hospital of Northern Theater CommandDepartment of Cardiology, Second Norman Bethune Hospital of Jilin UniversityAbstract Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but the underlying molecular interactions remain unclear. This study aims to identify the molecular mechanisms of ERS in AS pathogenesis to inform innovative diagnostic approaches and therapeutic targets for managing AS. GSE28829 and GSE43292—human early and advanced carotid atherosclerotic tissue samples—were obtained from the Gene Expression Omnibus database. Endoplasmic reticulum stress-related genes (ERSRGs) were obtained from GeneCards. Differential gene expression and weighted gene co-expression network analyses were conducted to identify genes associated with atherosclerosis, and intersection with ER-related genes revealed three ERSRGs (i.e. CTSB, LYN, and CYBB) associated with advanced atherosclerotic plaque. These three ERSRGs exhibited associations with various immune cells. Additionally, the three ERSRGs were upregulated in human atherosclerotic tissues, mouse models of progressive atherosclerotic lesions, and in vitro macrophage models. In conclusion, this study identified CTSB, LYN, and CYBB as potentially critical ERSRGs associated with advanced atherosclerotic plaque, demonstrating their good diagnostic utility and offering novel insights into the potential pathobiology of AS progression, paving the way for exploring innovative therapeutic targets.https://doi.org/10.1038/s41598-024-83925-zAtherosclerosisEndoplasmic reticulum stressImmune infiltrationBioinformatics analysis
spellingShingle Ning Zhao
Dan Liu
Haixu Song
Xiaolin Zhang
Chenghui Yan
Yaling Han
Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
Scientific Reports
Atherosclerosis
Endoplasmic reticulum stress
Immune infiltration
Bioinformatics analysis
title Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
title_full Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
title_fullStr Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
title_full_unstemmed Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
title_short Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque
title_sort identification of critical endoplasmic reticulum stress related genes in advanced atherosclerotic plaque
topic Atherosclerosis
Endoplasmic reticulum stress
Immune infiltration
Bioinformatics analysis
url https://doi.org/10.1038/s41598-024-83925-z
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AT haixusong identificationofcriticalendoplasmicreticulumstressrelatedgenesinadvancedatheroscleroticplaque
AT xiaolinzhang identificationofcriticalendoplasmicreticulumstressrelatedgenesinadvancedatheroscleroticplaque
AT chenghuiyan identificationofcriticalendoplasmicreticulumstressrelatedgenesinadvancedatheroscleroticplaque
AT yalinghan identificationofcriticalendoplasmicreticulumstressrelatedgenesinadvancedatheroscleroticplaque